Focus of Research for Clinicians

As an update to a 2007 report, a systematic review of 248 clinical studies published between January 1980 and January 2011 examined the comparative effectiveness, benefits, and adverse effects of second-generation antidepressants for adults with depression. This review did not cover nonpharmaceutical treatments for depression, the comparative effectiveness of first-generation antidepressants, or the use of second-generation antidepressants in treating other axis 1 disorders including substance use disorders, bipolar disorder, bulimia nervosa, or schizophrenia. The full report is available at www.effectivehealthcare.ahrq.gov/secondgenantidep.cfm. This summary is provided to inform discussions of options with patients and to assist in decisionmaking along with consideration of a patient’s values and preferences. Reviews of evidence should not be construed to represent clinical recommendations or guidelines.

Background

Depressive disorders, including major depressive disorder (MDD), dysthymia, and subsyndromal depression, affect approximately one in five people in the United States. Pharmacotherapy dominates the medical management of depressive disorders. Most first- and second-generation antidepressants both have about a 60-percent response rate when used to treat adults with MDD. However, first-generation antidepressants often have intolerable side effects and a high risk for harm when taken in excess or in combination with certain medications. Second-generation antidepressants have a more favorable side-effect profile and thus play a prominent role in managing patients with MDD.

The 2007 comparative effectiveness review on second-generation antidepressants summarized the available evidence on 12 medications (see Table 1) and their comparative efficacy, effectiveness, and adverse effects for treating adults with depression, maintaining remission, and treating accompanying symptoms such as anxiety, insomnia, and chronic pain. This updated review includes additional comparative data, one new medication, and additional studies on formulas of included medications.

Conclusion

New evidence included in the current review continues to support the original conclusions from the 2007 review, namely that second-generation antidepressants used to treat MDD in adults have similar effectiveness, efficacy, and effects on quality of life. Some clinically significant differences among individual drugs do exist with respect to onset of action and adverse effects, which may affect treatment choices. For example, mirtazapine has a faster onset of action but is associated with greater weight gain. Also, bupropion has fewer sexual side effects than many comparators. More research is needed to evaluate whether the benefits or adverse effects of second-generation antidepressants differ in subgroups or in populations with accompanying symptoms such as anxiety, insomnia, or chronic pain.

This summary was prepared by the John M. Eisenberg Center for Clinical Decisions and Communications Science at Baylor College of Medicine, Houston, TX. It was written by Andrea Humphries, Ph.D., Thomas Workman, Ph.D., Rayan Al Jurdi, M.D., and Michael Fordis, M.D.